Familial Pityriasis Rubra Pilaris Is Caused by Mutations in CARD14
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- 作者：Dana Fuchs-Telem ; Ofer Sarig ; Maurice?A.M. van?Steensel ; Ofer Isakov ; Shirli Israeli ; Janna Nousbeck ; Katharina Richard ; Veronique Winnepenninckx ; Marigje Vernooij ; Noam Shomron ; Jouni Uitto ; Philip Fleckman ; Gabriele Richard ; Eli Sprecher
- 刊名：The American Journal of Human Genetics
- 出版年：2012
- 出版时间：13 July, 2012
- 年：2012
- 卷：91
- 期：1
- 页码：163-170
- 全文大小：1331 K
文摘
Pityriasis rubra pilaris (PRP) is a papulosquamous disorder phenotypically related to psoriasis. The disease has been occasionally shown to be inherited in an autosomal-dominant fashion. To identify the genetic cause of familial PRP, we ascertained four unrelated families affected by autosomal-dominant PRP. We initially mapped PRP to 17q25.3, a region overlapping with psoriasis susceptibility locus 2 (PSORS2 [MIM ]). Using a combination of linkage analysis followed by targeted whole-exome sequencing and candidate-gene screening, we identified three different heterozygous mutations in CARD14, which encodes caspase recruitment domain family, member 14. CARD14 was found to be specifically expressed in the skin. CARD14 is a known activator of nuclear factor kappa B signaling, which has been implicated in inflammatory disorders. Accordingly, CARD14 levels were increased, and p65 was found to be activated in the skin of PRP-affected individuals. The present data demonstrate that autosomal-dominant PRP is allelic to familial psoriasis, which was recently shown to also be caused by mutations in CARD14.